Effect of non-spherical shape of dry powder aerosol drugs on their airway deposition distribution

In the majority of aerosol drug deposition modelling efforts, the particles are approximated by regular spheres. However, microscope images acquired after drug formulation available in the open literature suggest that their shape is not regular in most of the cases. This work aimed to combine experimental measurements and numerical simulations to reveal the shape factors of the particles of commercialized aerosol drugs and the effect of non-sphericity on the lung deposition distribution of these drugs. Aerosol particles of Bretaris® Genuair®, Buventol® Easyhaler® and Trelegy® Ellipta® were collected on the stages of a Next Generation Impactor after their emission from the dry powder inhalers. The samples were analyzed using scanning electron microscopy techniques. Aspect ratios and dynamic shape factors characteristic of particles in the size fractions representing each impactor stage were determined. Computer modelling of their airway deposition was performed by both neglecting and considering their irregular shape. The results of particle size measurements revealed that there was no size-specific shape factor of the particles, as they could be well characterized by a global shape factor. Although there was some inter-drug difference in terms of shape factors, the values were quite close to unity (usually between 1.02 and 1.06), except for the fiber-shaped particles representing a minority in the composition of Trelegy® Ellipta®, which could be characterized by shape factors of around 1.6. The results of computer simulations of deposition distribution indicate that neglecting the irregular shape does not lead to a major distortion of the simulation results unless fiber-shaped particles are also present after the formulation.